Dorema Aucheri Extract Modulates Unfolded Protein Response Pathways in Streptozotocin-Induced Diabetic Rats: A Protective Role Against Hepatic Damage.

PURPOSE: Endoplasmic reticulum stress (ERS) plays a pivotal role in the development of diabetes-induced liver damage. Under elevated ERS, the unfolded protein response (UPR) balances cellular survival and death. There may be a preventive effect of herbal extracts against problems associated with diabetes. In this study, the effects of a hydroalcoholic extract from Dorema aucheri on liver damage, ERS, and UPR in diabetic rats were assessed. METHODS: There were five groups of rats, each including six rats. A 60 mg/kg intraperitoneal injection of streptozotocin (STZ) was used to cause diabetes. Every day, 1 mL of normal saline was given to the control groups, who were normal and diabetic. For 28 days, three diabetic groups were given oral gavage doses of 250/500 mg/kg of D. aucheri extract and 500 mg/kg of metformin daily. Serum and liver samples were used to assess blood glucose, liver enzymes, oxidative stress, inflammatory markers, and antioxidant levels after treatment. Furthermore, liver tissue pathology, stereology, and gene expression were examined. RESULTS: Compared to the diabetic groups, the treated groups exhibited a significant decrease in oxidative stress, inflammatory markers, liver enzymes, blood glucose, and increased antioxidant capacity. They significantly reduced mRNA levels of proapoptotic markers (CHOP, caspase-9, and NF-κB) and increased GRP78, XBP1s, and BCL2 expression, suggesting attenuation of apoptosis and modulation of UPR-related gene expression. CONCLUSION: D. aucheri extract may modulate UPR- and apoptosis-related pathways, alleviate ERS, and potentially reduce diabetes-associated complications in STZ-induced diabetic rats. However, further mechanistic and translational studies are required to confirm these findings and evaluate their clinical relevance.